First-in-class Therapy for Heart Failure with Preserved Ejection Fraction

Baker Heart and Diabetes Institute Background
Heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure, is estimated to affect 1.1 to 5.5% of the general population1 (at least 85 million people worldwide). Patients with HFpEF are commonly very symptomatic, with an elevated risk of rehospitalization and reduced quality of life due to its complex pathophysiology and the lack of proven effective therapies. With a rapidly increasing prevalence (AGR +2.6%), the management of patients with HFpEF is extremely challenging and associated with a high economic burden (>$3B in Australia only).
Inflammation is a critical contributor of HFpEF, being a key driver of cardiac fibrosis and therefore cardiac dysfunction. Breaking down the pathogenesis of such underlying mechanisms of HFpEF constitutes a promising therapeutic target that attracted intense research and development interest in recent years.
Technology Overview
The Baker Institute researchers have developed a family of anti-inflammatory compounds and dual inhibitors of p38-MAPK and its upstream pathway (receptor tyrosine kinase), reducing both inflammation and fibrosis. The lead compound, VCP979, is a small molecule that possesses many drug-like proprieties and a low toxicity profile. VCP979 ability to reduce inflammation, hypertrophy and fibrosis has been well demonstrated in vitro () and in different animal models. One-week post-myocardial infarction, oral administration of VCP979 (twice a day for 4 weeks – 50mg/kg/day) reduced inflammation as well as fibrosis and improved cardiac function in mice (); while ACE inhibitor (treatment generally prescribed to HFpEF patients) did not significantly improve cardiac function and inflammation markers in the experimental setting. Recent results showed similar effects of VCP979 in a mouse model of HFpEF, with a reduction in inflammation and fibrosis in both young and old animals ().
Stage of Development

Proof of concept: preclinical data available (in vitro & in vivo).
PK/PD and toxicology: preclinical data available (in vitro & in vivo).


Potent anti-inflammatory and anti-fibrotic activity
Improves cardiac function
Soluble small molecule, orally bioavailable, effective at a low dose, well-tolerated
Portfolio of 100+ patented analogs
Privileged access to various established animal models, cardiology core facility and an internationally recognized team successful in the generation of IP leading to commercial and clinical outcomes


Heart failure
Myocardial infarction
Adaptation for other conditions with inflammation and fibrosis

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